Sustained bursts of automatic weapons fire and powerful single shots rattled into the square starting at around 4 a.m., and was continuing more than an hour later.
Protest organizer Mustafa el-Naggar said he saw the bodies of three dead protesters being carried toward an ambulance. He said the gunfire came from at least three locations off in the distance and that the Egyptian military, which has ringed the square with tank squads for days to try to keep some order, did not intervene.
Footage from AP Television News showed two bodies being dragged from the scene. The health minister did not answer a phone call seeking confirmation of the deaths.
Throughout Wednesday, Mubarak supporters charged into the square on horses and camels brandishing whips while others rained firebombs from rooftops in what appeared to be an orchestrated assault against protesters trying to topple Egypt's leader of 30 years. Three people died in that earlier violence and 600 were injured.
The protesters accused Mubarak's regime of unleashing a force of paid thugs and plainclothes police to crush their unprecedented nine-day-old movement, a day after the 82-year-old president refused to step down. They showed off police ID badges they said were wrested from their attackers. Some government workers said their employers ordered them into the streets.
Mustafa el-Fiqqi, a top official from the ruling National Democratic Party, told The Associated Press that businessmen connected to the ruling party were responsible for what happened.
The notion that the state may have coordinated violence against protesters, who had kept a peaceful vigil in Tahrir Square for five days, prompted a sharp rebuke from the Obama administration.
"If any of the violence is instigated by the government, it should stop immediately," said White House Press Secretary Robert Gibbs.
The clashes marked a dangerous new phase in Egypt's upheaval: the first significant violence between government supporters and opponents. The crisis took a sharp turn for the worse almost immediately after Mubarak rejected the calls for him to give up power or leave the country, stubbornly proclaiming he would die on Egyptian soil.
His words were a blow to the protesters. They also suggest that authorities want to turn back the clock to the tight state control enforced before the protests began.
Mubarak's supporters turned up on the streets Wednesday in significant numbers for the first time. Some were hostile to journalists and foreigners. Two Associated Press correspondents and several other journalists were roughed up in Cairo. State TV had reported that foreigners were caught distributing anti-Mubarak leaflets, apparently trying to depict the movement as foreign-fueled.
After midnight, 10 hours after the clashes began, the two sides were locked in a standoff at a street corner, with the anti-Mubarak protesters hunkered behind a line of metal sheets hurling firebombs back and forth with government backers on the rooftop above. The rain of bottles of flaming gasoline set nearby cars and wreckage on the sidewalk ablaze.
The scenes of mayhem were certain to add to the fear that is already running high in this capital of 18 million people after a weekend of looting and lawlessness and the escape of thousands of prisoners from jails in the chaos.
Soldiers surrounding Tahrir Square fired occasional shots in the air throughout the day but did not appear to otherwise intervene in the fierce clashes and no uniformed police were seen. Most of the troops took shelter behind or inside the armored vehicles and tanks stationed at the entrances to the square.
"Why don't you protect us?" some protesters shouted at the soldiers, who replied they did not have orders to do so and told people to go home.
"The army is neglectful. They let them in," said Emad Nafa, a 52-year-old among the protesters, who for days had showered the military with affection for its neutral stance.
Some of the worst street battles raged near the Egyptian Museum at the edge of the square. Pro-government rioters blanketed the rooftops of nearby buildings and hurled bricks and firebombs onto the crowd below - in the process setting a tree ablaze inside the museum grounds. Plainclothes police at the building entrances prevented anti-Mubarak protesters from storming up to stop them.
The two sides pummeled each other with chunks of concrete and bottles at each of the six entrances to the sprawling plaza, where 10,000 anti-Mubarak protesters tried to fend off more than 3,000 attackers who besieged them. Some on the pro-government side waved machetes, while the square's defenders filled the air with a ringing battlefield din by banging metal fences with sticks.
In one almost medieval scene, a small contingent of pro-Mubarak forces on horseback and camels rushed into the anti-government crowds, trampling several people and swinging whips and sticks. Protesters dragged some riders from their mounts, throwing them to the ground and beating their faces bloody. The horses and camels appeared to be ones used to give tourists rides around Cairo.
Dozens of men and women pried up pieces of the pavement with bars and ferried the piles of ammunition in canvas sheets to their allies at the front. Others directed fighters to streets needing reinforcements.
The protesters used a subway station as a makeshift prison for the attackers they managed to catch. They tied the hands and legs of their prisoners and locked them inside. People grabbed one man who was bleeding from the head, hit him with their sandals and threw him behind a closed gate.
Some protesters wept and prayed in the square where only a day before they had held a joyous, peaceful rally of a quarter-million, the largest demonstration so far.
Egyptian Health Minister Ahmed Sameh Farid said three people died and at least 611 were injured in Tahir Square. One of those killed fell from a bridge near the square; Farid said the man was in civilian clothes but may have been a member of the security forces.
Farid did not say how the other two victims, both young men, were killed. It was not clear whether they were government supporters or anti-Mubarak demonstrators.
After years of tight state control, protesters emboldened by the uprising in Tunisia took to the streets on Jan. 25 and mounted a once-unimaginable series of demonstrations across this nation of 80 million. For the past few days, protesters who camped out in Tahrir Square reveled in a new freedom - publicly expressing their hatred for the Mubarak regime.
"After our revolution, they want to send people here to ruin it for us," said Ahmed Abdullah, a 47-year-old lawyer in the square.
Another man shrieked through a loudspeaker: "Hosni has opened the door for these thugs to attack us."
The pressure for demonstrators to clear the square mounted throughout the day, beginning early when a military spokesman appeared on state TV and asked them to disperse so life in Egypt could get back to normal.
It was a change in attitude by the army, which for the past few days had allowed protests to swell with no interference and even made a statement saying they had a legitimate right to demonstrate peacefully.
Then the regime began to rally its supporters in significant numbers for the first time, demanding an end to the protest movement. Some 20,000 Mubarak supporters held an angry but mostly peaceful rally across the Nile River from Tahrir, responding to calls on state TV.
They said Mubarak's concessions were enough. He has promised not to run for re-election in September, named a new government and appointed a vice president for the first time, widely considered his designated successor.
They waved Egyptian flags, their faces painted with the black-white-and-red national colors, and carried a large printed banner with Mubarak's face as police officers surrounded the area and directed traffic. They cheered as a military helicopter swooped overhead.
They were bitter at the jeers hurled at Mubarak.
"I feel humiliated," said Mohammed Hussein, a 31-year-old factory worker. "He is the symbol of our country. When he is insulted, I am insulted."
Sayyed Ramadan, a clothing vendor said: "Eight days with no security, safety, food or drink. I earn my living day by day. The president didn't do anything. It is shame that we call him a dog."
Emad Fathi, 35, works as a delivery boy but since the demonstrations, he has not gone to work.
"I came here to tell these people to leave," he said. "The mosques were calling on people to go and support Mubarak," he said.
The anti-Mubarak movement has vowed to intensify protests to force him out by Friday.
State TV said Vice President Omar Suleiman called "on the youth to heed the armed forces' call and return home to restore order." From the other side, senior anti-Mubarak figure Mohamed ElBaradei demanded the military "intervene immediately and decisively to stop this massacre."
Secretary of State Hillary Rodham Clinton spoke with Suleiman to condemn the violence and urge Egypt's government to hold those responsible for it accountable, State Department spokesman P.J. Crowley said.
Protesters had maintained a round-the-clock, peaceful vigil in Tahrir Square since Friday night, when the military was first deployed and police largely vanished from the streets.
After celebrating their biggest success yet in Tuesday's demonstration, the crowd thinned out overnight. By morning a few thousand protesters remained. Mubarak supporters began to gather at the edges of the square a little after noon, and protesters formed a human chain to keep them out.
In the early afternoon, around 3,000 pro-government demonstrators broke through and surged among the protesters, according to an Associated Press reporter at the scene.
They tore down banners denouncing the president, fistfights broke out, and protesters grabbed Mubarak posters from the hands of the supporters and ripped them to pieces.
From there, it escalated into outright street battles as hundreds poured in to join each side.
The battle lines at each of the entrances surged back and forth for hours. Each side's fighters stretched across the width of the four-lane divided boulevard, hiding behind abandoned trucks and holding sheets of corrugated metal as shields from the hail of stones.
At the heart of the square, young men with microphones sought to keep up morale. "Stand fast, reinforcements are on the way," said one. "Youth of Egypt, be brave." Groups of bearded men lined up to recite Muslim prayers before taking their turn in the line of fire.
Bloodied young men staggered or were carried into makeshift clinics set up in mosques and alleyways by the anti-government side.
Women and men stood ready with water, medical cotton and bandages as each wave returned. Scores of wounded were carried to a makeshift clinic at a mosque near the square and on other side streets, staffed by doctors in white coats. One man with blood coming out of his eye stumbled into a side-street clinic.
As night fell, some protesters went to get food, a sign they plan to dig in for a long siege. Hundreds more people from the impoverished district of Shubra showed up later as reinforcements.
Wednesday's events suggest the regime aims to put an end of the unrest to let Mubarak shape the transition as he chooses over the next months. Mubarak has offered negotiations with protest leaders over democratic reforms, but they have refused any talks until he steps down.
As if to show the public the crisis was ending, the government began to reinstate Internet service after days of an unprecedented cutoff. State TV announced the easing of a nighttime curfew, which now runs from 5 p.m. to 7 a.m. instead of 3 p.m. to 8 a.m.
AP correspondents Sarah El Deeb, Hamza Hendawi, Diaa Hadid, Lee Keath, Michael Weissenstein and Maggie Michael contributed to this report.